Since many of melanoma antigens are expressed in normal melanocytes, and thus are self-antigens regulated by self-tolerance mechanisms, successful anti-melanoma T cell responses are difficult to generate. In successful immunotherapies for melanoma, an immune-mediated skin depigmentation is often observed with tumor regression. Thus, mechanisms that govern autoimmune vitiligo may also be useful for developing anti-melanoma adoptive transfer strategies. Since the Ags implicated in vitiligo and melanoma are self-Ags, understanding how the autoreactive anti-melanocyte specific T cells escape peripheral tolerance and efficiently destroy melanocytes may result in improved anti-melanoma T cell therapies. Autoimmune vitiligo development is achieved by sublethal irradiation/IL-2 plus T cell transfer and autoantigen-specific T cell receptor transgenic expression in mice. Therefore, the aims of the proposal function to determine: the requirements for vitiligo induction by self-reactive CD8+ T cells and capacity of intrinsic factors to rescue autoreactive T cells and promote anti-melanoma responses. [unreadable] [unreadable] [unreadable]